The proposed project is to study factors controlling the proliferation and maturation of granulocytes in vivo and in vitro. The major emphasis is directed toward the study of in vitro proliferation of colonies of granulocytic and mononuclear cells from marrow and blood of animals and man. Colonies are cultured in a soft gel system (agar or methylcellulose) in the presence of a colony stimulating activity (CSA). Human and animal cells will also be cultured in liquid suspension and in millipore chambers. Studies will include the following: 1) to determine CSA activity in vivo, 2) to determine the mechanism of action of leukopenia in viral diseases, 3) to determine the ability of various agents to protect marrow against cytotoxic agents, 4) to study the effect of BCG on granulocyte and macrophage production, 5) to study the pattern of colony formation in patients with Polycythemia Vera, myelofibrosis and leukemia, 6) to study the pattern of in vitro colony formation in acute leukemia and response to therapy, 7) to attempt to isolate and purify granulocyte progenitor cell (CFU-C) population in order to study the mechanism of action of CSA in inducing cell proliferation and maturation. BIBLIOGRAPHIC REFERENCES: Ruscetti, F.W., Cypess, R.H. and Chervenick, P.A. Specific Release of Neutrophilic and Eosinophilic Stimulating Factors from Sensitized Lymphocytes. Blood, 1976, in press. Gall, J.A., Boggs, D.R., Chervenick, P.A., Pan, S. and Fleming, R.B. Discordant Patterns of Chromosome Changes and Myeloblast Proliferation During the Terminal Phase of Chronic Myeloid Leukemia. Blood, 1976, in press.